P. FALCIPARUM SEQUESTRATION: GETTING OUT OF THE STICKY SITUATION ONE BOND AT A TIME
Ying, Bena Lim1,2, Juzar Yahya Thingna2, Fang Kong2, Chwee Teck Lim1,2, Jianshu Cao2,3
1National University of Singapore, Singapore;
2Singapore MIT Alliance for Research and Technology, Singapore;
3Massachusetts Institute of Technology, USA
Sequestration of Plasmodium falciparum infected red blood cells (iRBCs) in host microvasculature is associated with multiple organ failure and cerebral malaria. Of the several endothelial receptors that iRBCs adhere to, CD36 and ICAM-1 upregulation
has been correlated with severe disease pathology. Interestingly, ICAM-1 is able to mediate the rolling of iRBCs on endothelium and is also the only receptor identified to correlate with cerebral malaria. We first probed iRBC/ICAM-1 and iRBC/CD36 bonds at a single molecule level to understand the fundamental interactions between iRBCs and these endothelial ligands. Force spectroscopy experiments revealed catch bond interactions between iRBCs and ICAM-1. In contrast, slip bonds were formed with CD36. These findings explain why ICAM-1 mediates the rolling of iRBCs in in-vitro experiments while CD36 facilitates stationary adhesion. Next, we studied the effects of temperature on these interactions to provide greater insight on how the tertian febrile cycle experienced by a malaria infected patient may affect iRBC-ligand interactions. Understanding iRBC-ligand interactions at the single bond level can potentially help to unravel the mechanics involved in cytoadhesion, bringing us a step closer towards tackling this sticky problem.